AVR-RD-02 / AVROBIO - LARVOL DELTA

Preliminary safety, pharmacodynamic and clinical efficacy report from the subjects observed for up to 30 months post-treatment in the Guard1 clinical trial: a first in-human, phase 1/2 study evaluating AVR-RD-02, a Gaucher disease autologous hematopoietic stem cell (HSC)-based gene therapy (ESGCT 2023) - No abstract available

Clinical • Gene therapy • P1/2 data • PK/PD data • Gaucher Disease • Gene Therapies • Genetic Disorders • Metabolic Disorders

A Long-Term Follow-up Study of Subjects With Gaucher Disease Who Previously Received AVR-RD-02 (clinicaltrials.gov) - P=N/A | N=4 | Terminated | Sponsor: AVROBIO | N=16 ➔ 4 | Trial completion date: Dec 2038 ➔ Aug 2023 | Enrolling by invitation ➔ Terminated | Trial primary completion date: Dec 2038 ➔ Aug 2023; This study was voluntarily terminated due to a business decision not to proceed, and not due to any safety or efficacy issue

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Gaucher Disease • Gene Therapies • Genetic Disorders • Metabolic Disorders • Type 1 Gaucher Disease

Lentiviral Vector Gene Therapy - The Guard1 Trial of AVR-RD-02 for Subjects With Type 1 Gaucher Disease (clinicaltrials.gov) - P1/2 | N=7 | Terminated | Sponsor: AVROBIO | N=16 ➔ 7 | Trial completion date: Dec 2023 ➔ Aug 2023 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2023 ➔ Aug 2023; This study was voluntarily terminated due to a business decision not to proceed, and not due to any safety or efficacy issue

Enrollment change • Gene therapy • Trial completion date • Trial primary completion date • Trial termination • Viral vector • Gaucher Disease • Gene Therapies • Genetic Disorders • Metabolic Disorders • Type 1 Gaucher Disease

An Efficacy and Safety Study of AVR-RD-02 Compared to Enzyme Replacement Therapy for Treatment of Gaucher Disease Type 3 (clinicaltrials.gov) - P2/3 | N=0 | Withdrawn | Sponsor: AVROBIO | N=40 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Gene therapy • Trial withdrawal • Gaucher Disease • Gene Therapies • Genetic Disorders • Metabolic Disorders

An Efficacy and Safety Study of AVR-RD-02 Compared to Enzyme Replacement Therapy for Treatment of Gaucher Disease Type 3 (clinicaltrials.gov) - P2/3 | N=40 | Not yet recruiting | Sponsor: AVROBIO

Gene therapy • New P2/3 trial • Gaucher Disease • Gene Therapies • Genetic Disorders • Metabolic Disorders

SUSTAINED IMPROVEMENT OF CLINICAL CNS AND SOMATIC FEATURES OF TYPE 3 GAUCHER DISEASE AFTER HAEMATOPOIETIC STEM CELL (HSC) GENE THERAPY: A FIRST-IN-WORLD REPORT (EBMT 2023) - "Conditioning with targeted dose of busulfan preceded infusion of AVR-RD-02. This case-report shows the safety of an ex-vivo lenti viral HSC gene therapy approach to neuronopathic Gaucher disease. Visceral efficacy is demonstrated by sustained peripheral enzyme activity over a year post infusion. The data presented mimics the historical experience of using HSCT in lysosomal storage disorders with a better side effect and tolerability profile."

Clinical • Gene therapy • Bone Marrow Transplantation • CNS Disorders • Epilepsy • Febrile Neutropenia • Gaucher Disease • Gene Therapies • Genetic Disorders • Hematological Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Neutropenia • Pulmonary Disease • Rare Diseases • Respiratory Diseases • CD34 • GBA

A Long-Term Follow-up Study of Subjects With Gaucher Disease Who Previously Received AVR-RD-02 (clinicaltrials.gov) - P=N/A | N=16 | Enrolling by invitation | Sponsor: AVROBIO | Trial completion date: Oct 2037 ➔ Dec 2038 | Trial primary completion date: Jul 2037 ➔ Dec 2038

Trial completion date • Trial primary completion date • Gaucher Disease • Gene Therapies • Genetic Disorders • Metabolic Disorders • Type 1 Gaucher Disease

A Follow-up Study of Subjects With Type 1 Gaucher Disease Who Previously Received AVR-RD-02 (clinicaltrials.gov) - P=N/A; N=16; Enrolling by invitation; Sponsor: AvroBio; Not yet recruiting ➔ Enrolling by invitation

Clinical • Enrollment open • Gaucher Disease • Gene Therapies • Genetic Disorders • Metabolic Disorders • Type 1 Gaucher Disease • MRI

[VIRTUAL] The GuardOne clinical trial: a first inhuman, openlabel, multinational phase 1/2 study of AVRRD02 ex vivo lentiviral vector, autologous gene therapy for Gaucher disease (ESGCT 2021) - "The first patient has been dosed in GuardOne and the trial is active in the US, Canada and Australia, with a site in Israel to open in 2021. Early clinical data will be provided."

P1/2 data • Preclinical • Gaucher Disease • Gene Therapies • Genetic Disorders • Metabolic Disorders • Transplantation • Type 1 Gaucher Disease • CD34 • GBA

Lentiviral Vector Gene Therapy - The GuardOne Trial of AVR-RD-02 for Subjects With Type 1 Gaucher Disease (clinicaltrials.gov) - P1/2; N=16; Recruiting; Sponsor: AvroBio; Trial completion date: Sep 2022 ➔ Dec 2023; Trial primary completion date: May 2021 ➔ Dec 2023

Clinical • Preclinical • Trial completion date • Trial primary completion date • Gaucher Disease • Gene Therapies • Genetic Disorders • Metabolic Disorders • Type 1 Gaucher Disease • MRI • PCR

[VIRTUAL] Preliminary Results from the Phase 1/2 GuardOne Trial: A First-in-Human Study of Ex Vivo Lentiviral Gene Therapy (AVR-RD-02) in People with Gaucher Disease Type 1 (ASGCT 2021) - "Patients receive a single round of personalized busulfan conditioning prior to AVR-RD-02 infusion in order to optimize genetically modified cell engraftment in the bone marrow and brain, while minimizing potential side effects. No unexpected trends or safety concerns were identified. Six-month data for Patient 1 will be reported in this presentation."

P1/2 data • Preclinical • Gaucher Disease • Gene Therapies • Genetic Disorders • Immunology • Inflammation • Metabolic Disorders • Type 1 Gaucher Disease • CD34 • GBA

A Follow-up Study of Subjects With Type 1 Gaucher Disease Who Previously Received AVR-RD-02 (clinicaltrials.gov) - P; N=16; Not yet recruiting; Sponsor: AvroBio

New trial • Gaucher Disease • Gene Therapies • Genetic Disorders • Metabolic Disorders • Type 1 Gaucher Disease • MRI

AVROBIO Reports Second Quarter 2020 Financial Results and Provides Business Update (Businesswire) - "AVROBIO's investigational gene therapy for Gaucher disease is being studied in the GuardOne clinical trial, a Phase 1/2 trial to evaluate the safety and efficacy in individuals with Gaucher disease type 1. The trial is expected to enroll eight to 16 patients between the ages of 18 and 35 who are treatment-naïve and on ERT. Patient 1 was dosed in AVROBIO’s global Phase 1/2 clinical trial in July 2020. Subsequent new patient dosing and enrollment timelines have been impacted by the COVID-19 pandemic. However, patient recruitment activities continue for our clinical sites in Australia and Canada. New clinical sites expected to open in the U.S. and Israel in the fourth quarter of the year."

Enrollment status • Trial status • Gaucher Disease • Genetic Disorders

AVROBIO Announces New Patients Dosed in Gaucher Disease and Cystinosis Clinical Trials (Businesswire) - "AVROBIO, Inc....today announced that the first patient has been dosed in the company’s GuardOne clinical trial, a Phase 1/2 investigational study evaluating AVR-RD-02 for Gaucher disease type 1....The company’s Phase 1/2 trial of AVR-RD-02 for Gaucher disease type 1 is currently recruiting patients in Australia and Canada, with new clinical sites expected to open in the U.S. and Israel by year-end....The trial will include both patients who are treatment-naïve and who are on ERT....Patient recruitment activities for AVROBIO’s Phase 2 FAB-201 trial for Fabry disease continue for clinical trial sites in Australia, Canada and the U.S."

Enrollment status • Trial status • Fabry Disease • Gaucher Disease • Genetic Disorders • Type 1 Gaucher Disease

10th World Orphan Drug Congress (WODC) (November 12-14, 2019 - Barcelona, Spain). (PubMed, Drugs Today (Barc)) - "A co-conference on Cell and Gene Therapy was also organized. This rare disease conference addressed many different challenges in the field with numerous discussions on how to improve cross-border communications, how to better identify patients and shorten their diagnosis time using new tools such as artificial intelligence and machine learning, as well as how to improve usage of patient data and patient empowerment."

Journal • Orphan drug

Phase 1/2 Lentiviral Vector Gene Therapy AVR-RD-02 for Subjects With Type 1 Gaucher Disease (clinicaltrials.gov) - P1/2; N=16; Recruiting; Sponsor: AvroBio

Clinical • New P1/2 trial

Preclinical data has AVR-RD-02 gene therapy on track for first trial in humans (Gaucher Disease News) - "Avrobio presented updated preclinical data for AVR-RD-02, its gene therapy candidate for Gaucher disease, and announced its plans to begin the first clinical studies in patients with type 1 disease in the second half of 2019....Researchers tested AVR-RD-02 both during early disease and later on, when spleen enlargement was already evident in mice. In both cases, the treatment led to a prominent reduction in glucocerebrosidase-accumulating cells — the so-called Gaucher cells — in clinically relevant tissues, including the bone marrow, spleen, liver, and thymus, as compared to mice that received a mock treatment."

New P1 trial • Preclinical

AVROBIO, Inc. reports fourth quarter and fiscal year 2018 financial results and provides business update (Businesswire) - "The AVR-RD-01 investigational gene therapy has been generally well tolerated with no serious adverse events (SAEs) related to the study drug, at up to 22- and 6-months follow-up in the Phase 1 and Phase 2 trials, respectively....AVROBIO received a no objection letter (NOL) from Health Canada to the clinical trial application (CTA) for GAU-201, its Phase 1/2 clinical trial of AVR-RD-02 in Gaucher disease."

Clinical • P1/2 data